Most, if not all, human diseases have one or more genetic factors that contribute to cause, likelihood of occurrence, severity, and response to existing or experimental treatments. There is a general perception that the ability to define a person's genetic makeup will lead to better health, improved treatments and a better understanding of risks to other family members. However, many genetic technologies increase uncertainty and confusion in the minds of patients, relatives, doctors, health insurers and others. The Penn CEER will define these issues better and offer suggestions for reducing the problems of uncertainty. The overall goal of the Center of Excellence for Ethical, Legal and Social Research at the University of Pennsylvania (Penn CEER) is to develop tools that will help consumers, professionals, policy makers and insurers understand and cope with the scope of certainty and uncertainty that genetic technologies engender. We propose to establish three cores to support transdisciplinary ELSI research and plan to study three situations at the outset. The initial studies will be: 1) To explore the evolution of prenatal screening for Down syndrome and cystic fibrosis carrier screening through a collaboration between historians of science, medical anthropologists, reproductive geneticists, prenatal care providers and women of reproductive age;2) To utilize the Penn Center of Excellence for Hereditary Hemorrhagic Telangiectasia to explore the impact of presymptomatic molecular testing on the economics of caring for people at risk, and patient and provider perceptions of the utility of and barriers to testing;and 3) To follow a cohort of African-American (and other minority) women who have been counseled for testing of BRCA1 and BRCA2 to assess the longer-term psychological, social, and medical impact of risk counseling and genetic testing on themselves and their family members, with a focus on uncertainty. As part of the first two projects, group deliberations in real time will be facilitated by our investigators in the Annenberg School for Communication to explore public perceptions about the results of the formal investigations. The results of each of the three initial projects, and additional studies supported by the CEER, will be considered for dissemination through the Research-to-Policy Core, directed by colleagues in the Leonard Davis Institute of Health Economics. The Training Core of the Penn CEER will provide postdoctoral stipends, through a competitive process, which will prepare fellows to obtain further funding to develop a career in ELSI research. Additionally, the Penn CEER will serve as a resource for other Penn faculty, for other CEERs, and for individuals, volunteer support groups, payers of health care services and investigators, for educating about the implications of genetic technologies in terms of the realms of certainty.